tbuckley/cabot-search huggingface dataset:
Recapitulation of Perturbed Striatal Gene Expression Dynamics of Donors’ Brains With Ventral Forebrain Organoids Derived From the Same Individuals With Schizophrenia
Authors: Tomoyo Sawada, André R. Barbosa, Bruno Araujo, Alejandra E. McCord, Laura D’Ignazio, Kynon J.M. Benjamin, Bonna Sheehan, Michael Zabolocki, Arthur Feltrin, Ria Arora, Anna C. Brandtjen, Joel E. Kleinman, Thomas M. Hyde, Cedric Bardy, Daniel R. Weinberger, Apuã C.M. Paquola, Jennifer A. Erwin
Journal: American Journal of Psychiatry (2023)

Schizophrenia is a brain disorder that originates during neurodevelopment and has complex genetic and environmental etiologies. Despite decades of clinical evidence of altered striatal function in affected patients, studies examining its cellular and molecular mechanisms in humans are limited. To explore neurodevelopmental alterations in the striatum associated with schizophrenia, the authors established a method for the differentiation of induced pluripotent stem cells (iPSCs) into ventral forebrain organoids (VFOs).
NLRP3 inflammasome in cognitive impairment and pharmacological properties of its inhibitors
Authors: Yi Xu, Yanling Yang, Xi Chen, Danling Jiang, Fei Zhang, Yao Guo, Bin Hu, Guohai Xu, Shengliang Peng, Lidong Wu, Jialing Hu
Journal: Translational Neurodegeneration (2023)

Abstract Cognitive impairment is a multifactorial and multi-step pathological process that places a heavy burden on patients and the society. Neuroinflammation is one of the main factors leading to cognitive impairment. The inflammasomes are multi-protein complexes that respond to various microorganisms and endogenous danger signals, helping to initiate innate protective responses in inflammatory diseases. NLRP3 inflammasomes produce proinflammatory cytokines (interleukin IL-1β and IL-18) by activating caspase-1. In this review, we comprehensively describe the structure and functions of the NLRP3 inflammasome. We also explore the intrinsic relationship between the NLRP3 inflammasome and cognitive impairment, which involves immune cell activation, cell apoptosis, oxidative stress, mitochondrial autophagy, and neuroinflammation. Finally, we describe NLRP3 inflammasome antagonists as targeted therapies to improve cognitive impairment.
Congenital lung malformations
Authors: Federica Pederiva, Steven S. Rothenberg, Nigel Hall, Hanneke Ijsselstijn, Kenneth K. Y. Wong, Jan von der Thüsen, Pierluigi Ciet, Reuven Achiron, Adamo Pio d’Adamo, J. Marco Schnater
Journal: Nature Reviews Disease Primers (2023)
Can the curse of mood disorders in COPD be lifted and enable pulmonary rehabilitation?
Authors: Rachael Evans, Gillian Doe
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>The negative results of the TANDEM study prompts us to consider how we can best manage mood disorders in #COPD and enable #pulmonaryrehabilitation. Approaches to enhance both patient and healthcare professional activation are needed.</b>https://bit.ly/3F3USVF
Earthquake disaster and respiratory health: lessons from Turkey and Syria in 2023
Authors: Yousser Mohammad, Hasan Bayram, Ozgecan Kayalar, Fabio Madonna, Isabella Annesi-Maesano
Journal: European Respiratory Journal (2023)

On 6 February 2023, a strong earthquake of 7.8 magnitude (Mw) hit the Southeast provinces of Turkey and Northwestern territories of Syria at 04:17 h local time (figure 1). The first shake was followed by another with a similar scale of 7.5 Mw, with more than 11 000 aftershocks recorded in the following days [1, 2]: the most powerful earthquakes in Turkey since 1939 [3]! Earthquake is a risk factor for respiratory health <https://bit.ly/3P8fSin>
Natural course of pollen‐induced allergic rhinitis from childhood to adulthood: A 20‐year follow up
Authors: Magnus Lindqvist, Katja Biering Leth‐Møller, Allan Linneberg, Inger Kull, Anna Bergström, Antonios Georgellis, Magnus P. Borres, Agneta Ekebom, Marianne van Hage, Erik Melén, Marit Westman
Journal: Allergy (2023)

Abstract Background Allergic rhinitis (AR) is one of the most common chronic diseases worldwide. There are limited prospective long‐term data regarding persistency and remission of AR. The objective of this study was to investigate the natural course of pollen‐induced AR (pollen‐AR) over 20 years, from childhood into early adulthood. Methods Data from 1137 subjects in the Barn/Children Allergi/Allergy Milieu Stockholm Epidemiologic birth cohort (BAMSE) with a completed questionnaire regarding symptoms, asthma, treatment with allergen immunotherapy (AIT) and results of allergen‐specific IgE for inhalant allergens at 4, 8, 16 and 24 years were analyzed. Pollen‐AR was defined as sneezing, runny, itchy or blocked nose; and itchy or watery eyes when exposed to birch and/or grass pollen in combination with allergen‐specific IgE ≥0.35kU A /L to birch and/or grass. Results Approximately 75% of children with pollen‐AR at 4 or 8 years had persistent disease up to 24 years, and 30% developed asthma. The probability of persistency was high already at low levels of pollen‐specific IgE. The highest rate of remission from pollen‐AR was seen between 16 and 24 years (21.5%); however, the majority remained sensitized. This period was also when pollen‐specific IgE‐levels stopped increasing and the average estimated annual incidence of pollen‐AR decreased from 1.5% to 0.8% per year. Conclusion Children with pollen‐AR are at high risk of persistent disease for at least 20 years. Childhood up to adolescence seems to be the most dynamic period of AR progression. Our findings underline the close cross‐sectional and longitudinal relationship between sensitization, AR and asthma.
Combining avidin with CD63 improves basophil activation test accuracy in classifying peanut allergy
Authors: Nicolas Castaño, Kaiser Chua, Abhinav Kaushik, Sungu Kim, Seth C. Cordts, Ceena D. Nafarzadegan, Grady H. Hofmann, Hana Seastedt, Jackson P. Schuetz, Diane Dunham, Ella S. Parsons, Mindy Tsai, Shu Cao, Manisha Desai, Sayantani B. Sindher, R. Sharon Chinthrajah, Stephen J. Galli, Kari C. Nadeau, Sindy K. Y. Tang
Journal: Allergy (2023)

Abstract Background Conventional basophil activation tests (BATs) measure basophil activation by the increased expression of CD63. Previously, fluorophore‐labeled avidin, a positively‐charged molecule, was found to bind to activated basophils, which tend to expose negatively charged granule constituents during degranulation. This study further compares avidin versus CD63 as basophil activation biomarkers in classifying peanut allergy. Methods Seventy subjects with either a peanut allergy ( N = 47), a food allergy other than peanut ( N = 6), or no food allergy ( N = 17) were evaluated. We conducted BATs in response to seven peanut extract (PE) concentrations (0.01–10,000 ng/mL) and four control conditions (no stimulant, anti‐IgE, fMLP (N‐formylmethionine‐leucyl‐phenylalanine), and anti‐FcεRI). We measured avidin binding and CD63 expression on basophils with flow cytometry. We evaluated logistic regression and XGBoost models for peanut allergy classification and feature identification. Results Avidin binding was correlated with CD63 expression. Both markers discriminated between subjects with and without a peanut allergy. Although small by percentage, an avidin + /CD63 − cell subset was found in all allergic subjects tested, indicating that the combination of avidin and CD63 could allow a more comprehensive identification of activated basophils. Indeed, we obtained the best classification accuracy (97.8% sensitivity, 96.7% specificity) by combining avidin and CD63 across seven PE doses. Similar accuracy was obtained by combining PE dose of 10,000 ng/mL for avidin and PE doses of 10 and 100 ng/mL for CD63. Conclusions Avidin and CD63 are reliable BAT activation markers associated with degranulation. Their combination enhances the identification of activated basophils and improves the classification accuracy of peanut allergy.
A Phase 2 Trial of Sibeprenlimab in Patients with IgA Nephropathy
Authors: Mohit Mathur, Jonathan Barratt, Bobby Chacko, Tak Mao Chan, Laura Kooienga, Kook-Hwan Oh, Manisha Sahay, Yusuke Suzuki, Muh Geot Wong, Jill Yarbrough, Jing Xia, Brian J.G. Pereira
Journal: New England Journal of Medicine (2023)

A proliferation-inducing ligand (APRIL) is implicated in the pathogenesis of IgA nephropathy. Sibeprenlimab is a humanized IgG2 monoclonal antibody that binds to and neutralizes APRIL.
HER2 overexpression predicts pathological T2 stage and improved survival in de novo muscle-invasive bladder cancer after immediate radical cystectomy: a retrospective cohort study
Authors: So Won Kim, Hoon Yu, Yoonjuong Kim, Kyenghyun Nam, Han Kyu Chae, Wook Nam, Dae-Woon Eom, Jong Yeon Park, Sung Jin Kim
Journal: International Journal of Surgery (2023)

Introduction: Human epidermal growth factor receptor type 2 (HER2) overexpression is a prognostic factor and a therapeutic target for breast cancer; however, anti-HER2 therapies are ineffective in patients with bladder cancer. We investigated the effect of HER2 overexpression (HER2 + ) on the prognosis of muscle-invasive bladder cancer (MIBC). Materials and methods: This retrospective cohort study included patients who underwent initial transurethral resection of bladder tumors between 2005 and 2013 and were registered in the Korea National Health Insurance Database, which provides data on overall survival (OS). Sixty-one patients with clinically non-metastatic de novo MIBC were included in this study. As a subgroup, 33 patients who underwent immediate radical cystectomy (RC) were analyzed. Univariate and multivariate Cox proportional hazards models were used to identify prognostic factors for survival. A multivariable binary logistic regression model was used to identify the favorable T stage. Results: Among the 61 patients with d-MIBC, 14 were HER2 + and 47 HER2 - . Age &lt; 70 years (HR: 0.312, CI: 0.16–0.59, P &lt; 0.001) and HER2 + status (HR: 0.40, CI: 0.19–0.85, P = 0.02) were favorable prognostic factors for OS after adjusting for clinical variables. In the RC subgroup, HER2 + status was a significant predictive factor for the pT2 stage (hazard ratio (HR): 36.8, CI: 4.83–797.41, P &lt; 0.01). Age &lt; 70 years (HR: 0.15, CI: 0.05–0.42, P &lt; 0.001) and HER2 + status (HR: 0.11, CI: 0.02–0.54, P = 0.01) were favorable prognostic factors for OS after adjusting for RC pathological variables. Conclusions: HER2 + status could be a marker for an indolent subset of MIBC and could predict favorable survival regardless of RC status. Moreover, HER2 + status not only consistently predicted favorable T stage after RC, but also predicted better survival than pathological outcomes.
Association between cerebrovascular disease and perioperative neurocognitive disorders: a retrospective cohort study
Authors: Lan Feng, Yuanhui Liu, PengFei Li, Hengjun Wan, Xiren Deng, Tingting Wang, Hong Fu, Xiaoxia Duan
Journal: International Journal of Surgery (2023)

Background: Previous studies have shown that patients with cerebrovascular disease (CVD) have a significantly increased risk of cognitive decline or dementia; however, the association between preoperative CVD and perioperative neurocognitive disorders (PNDs) remains unclear. This study aimed to explore the correlation between preoperative CVD and PNDs, as well as combine logistic regression and ROC curves to construct a clinical prediction PND model. Materials and Methods: This retrospective cohort study evaluated 13,899 surgical patients of a large-scale comprehensive hospital between January 2021 and January 2022 to explore the association between preoperative CVD and PNDs, with follow-up to monitor postoperative survival until February 28, 2023, unless the patient died. The study participants comprised all inpatients from the Bone and Joint Surgery, Spine Surgery, Urology, Hepatobiliary Surgery, Gastrointestinal Surgery, and Thoracic Surgery departments. Patients were classified into two groups: the CVD group with a confirmed diagnosis and the non-cerebrovascular disease (NCVD) group. The incidence of PNDs was measured, and potential associations between patient demographic information, preoperative comorbidities, and CVD, as well as the correlation between preoperative CVD and PNDs, were investigated by multivariate logistic regression analysis. Next, we constructed a clinical prediction PND model by drawing the receiver operating characteristic (ROC) curve. The postoperative survival of all patients was tracked, and a survival curve was constructed and incorporated into the Cox proportional hazard regression model to analyze the relationship between preoperative CVD and overall postoperative survival rate. Results: Of the included 13,899 patients, propensity score matching yielded 1006 patient pairs. Multivariate logistic regression analysis revealed that CVD was an independent risk factor for PNDs [Odds ratio: 10.193; 95% confidence interval: 7.454–13.938; P &lt;0.001]. Subsequently, we developed a clinical prediction model for PNDs by multivariate logistic regression analysis. The area under the ROC curve was 0.798 (95% CI: 0.765–0.830). The survival of 11,702 patients was followed up. Multivariate Cox hazard ratio regression analysis revealed that CVD affected the overall postoperative survival rate (Hazard ratio, 1.398; 95% confidence interval: 1.112–1.758; P ＜0.001). Conclusion: CVD was an independent risk factor for PNDs and affected the overall postoperative survival rate of surgical patients with preoperative CVD.
Metabolic syndrome and surgical complications: A systematic review and meta-analysis of 13 million individuals
Authors: Philip Norris, Jeff Gow, Thomas Arthur, Aaron Conway, Fergal J. Fleming, Nicholas Ralph
Journal: International Journal of Surgery (2023)

Background: Metabolic syndrome is characterised by the presence of at least three of the five following components: insulin resistance, obesity, chronic hypertension, elevated serum triglycerides and decreased high-density lipoprotein cholesterol concentrations. It is estimated to affect 1 in 3 people around the globe and reported to affect 46% of surgical patients. For people with metabolic syndrome who undergo surgery, an emerging body of literature points to significantly poorer postoperative outcomes compared with non-affected populations. The aim of this study is to review the current evidence on risks of surgical complications in patients with metabolic syndrome compared to those without metabolic syndrome. Methods: Systematic review and meta-analysis using PRISMA and AMSTAR reporting guidelines. Results: The meta-analysis included 63 studies involving 1,919,347 patients with metabolic syndrome and 11,248,114 patients without metabolic syndrome. Compared to individuals without the condition, individuals with metabolic syndrome were at an increased risk of mortality (OR 1.75 95% CIs [1.36-2.24]; P &lt;0.01); all surgical site infection types as well as dehiscence (OR 1.64 95% CIs [1.52 -1.77]; P &lt;0.01); cardiovascular complications (OR 1.56 95% CIs [1.41 -1.73]; P &lt;0.01) including myocardial infarction, stroke, cardiac arrest, cardiac arrythmias and deep vein thrombosis; increased length of hospital stay (MD 0.65 95% CIs [0.39-0.9]; P &lt;0.01); and hospital readmission (OR 1.55 95% CIs [1.41-1.71]; P &lt;0.01). Conclusion: Metabolic syndrome is associated with a significantly increased risk of surgical complications including mortality, surgical site infection, cardiovascular complications, increased length of stay and hospital readmission. Despite these risks and the high prevalence of metabolic syndrome in surgical populations there is a lack of evidence on interventions for reducing surgical complications in patients with metabolic syndrome. The authors suggest prioritising interventions across the surgical continuum that include (1) preoperative screening for metabolic syndrome; (2) surgical prehabilitation; (3) intraoperative monitoring and management; and (4) postoperative rehabilitation and follow-up.
A commentary on ‘Prognostic factors for acute vertebrobasilar artery occlusion–reperfusion: a multicenter retrospective cohort study’
Authors: Fenfei Wanggong, Jialin Baheti, Min Xu
Journal: International Journal of Surgery (2023)

aDepartment of Neurology, the Xinhua Hospital of Ili Kazak Autonomous Prefecture, Ili, Xinjiang, 835000, China bDepartment of Advanced Stroke Center, the Xinhua Hospital of Ili Kazak Autonomous Prefecture, Ili, Xinjiang, 835000, China All data in this manuscript is available and transparent for readers. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article Published online ■ ■ *Corresponding author. Address: Department of Advanced Stroke Center, the Xinhua Hospital of Ili Kazak Autonomous Prefecture, Ili, Xinjiang, 835000, China. E-mail address: [email protected] (M. Xu). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Diagnostic consistency between computed tomography and adrenal vein sampling of primary aldosteronism: leading to successful curative outcome after adrenalectomy; a retrospective study
Authors: Byung-Chang Kim, Hyun-Ki Yoon, Kye Jin Park, Gun Ha Kim, Shin Jeong Pak, Douk Kwon, Jae Won Cho, Won Woong Kim, Yu-mi Lee, Jung-Min Koh, Seung Hun Lee, Ki-Wook Chung, Tae-Yon Sung
Journal: International Journal of Surgery (2023)

Adrenal computed tomography (CT) is a useful tool for locating adrenal lesion in primary aldosteronism (PA) patients. However, adrenal vein sampling (AVS) is considered as a gold standard for subtype diagnosis of PA. The aim of this study was to investigate the consistency of CT and AVS for the diagnosis of PA subtypes and evaluate the concordance of surgical outcomes.
Long-term outcomes of surgical interventions for stress urinary incontinence: A systematic review and network meta-analysis
Authors: Yuanzhuo Chen, Chi Zhang, Shiqin Yang, Jiawei Chen, Liao Peng, Jie Chen, Hong Shen, Deyi Luo
Journal: International Journal of Surgery (2023)

Stress urinary incontinence is common among women, and surgical interventions have significantly improved patients' symptoms. The long-term effectiveness of these surgeries is increasingly drawing attention, yet it remains sparsely documented in the literature.
Single-cell epigenetic, transcriptional, and protein profiling of latent and active HIV-1 reservoir revealed that IKZF3 promotes HIV-1 persistence
Authors: Yulong Wei, Timothy C. Davenport, Jack A. Collora, Haocong Katherine Ma, Delia Pinto-Santini, Javier Lama, Ricardo Alfaro, Ann Duerr, Ya-Chi Ho
Journal: Immunity (2023)
Higher MDMX expression was associated with hypomethylating agent resistance and inferior survival in MDS patients, inferring it a potential therapeutic target
Authors: Yu-Hung Wang, Chien-Chin Lin, Kristian Gurashi, Bettina Wingelhofer, Fabio M. R. Amaral, Chi-Yuan Yao, Hsin Ting Hsieh, Ming Chih Liu, Hsin-An Hou, Wen-Chien Chou, Kiran Batta, Daniel H. Wiseman, Hwei-Fang Tien
Journal: Leukemia (2023)
Targeting lysine demethylase 6B ameliorates ASXL1 truncation-mediated myeloid malignancies in preclinical models
Authors: Guo Ge, Peng Zhang, Pinpin Sui, Shi Chen, Hui Yang, Ying Guo, Ivan P. Rubalcava, Asra Noor, Caroline R. Delma, Joel Agosto-Peña, Hui Geng, Edward A. Medina, Ying Liang, Stephen D. Nimer, Ruben Mesa, Omar Abdel-Wahab, Mingjiang Xu, Feng-Chun Yang
Journal: Journal of Clinical Investigation (2023)

ASXL1 mutation frequently occurs in all forms of myeloid malignancies and is associated with aggressive disease and poor prognosis. ASXL1 recruits Polycomb repressive complex 2 (PRC2) to specific gene loci to repress transcription through trimethylation of histone H3 on lysine 27 (H3K27me3). ASXL1 alterations reduce H3K27me3 levels, which results in leukemogenic gene expression and the development of myeloid malignancies. Standard therapies for myeloid malignancies have limited efficacy when mutated ASXL1 is present. We discovered upregulation of lysine demethylase 6B (KDM6B), a demethylase for H3K27me3, in ASXL1-mutant leukemic cells, which further reduces H3K27me3 levels and facilitates myeloid transformation. Here, we demonstrated that heterozygous deletion of Kdm6b restored H3K27me3 levels and normalized dysregulated gene expression in Asxl1Y588XTg hematopoietic stem/progenitor cells (HSPCs). Furthermore, heterozygous deletion of Kdm6b decreased the HSPC pool, restored their self-renewal capacity, prevented biased myeloid differentiation, and abrogated progression to myeloid malignancies in Asxl1Y588XTg mice. Importantly, administration of GSK-J4, a KDM6B inhibitor, not only restored H3K27me3 levels but also reduced the disease burden in NSG mice xenografted with human ASXL1-mutant leukemic cells in vivo. This preclinical finding provides compelling evidence that targeting KDM6B may be a therapeutic strategy for myeloid malignancies with ASXL1 mutations.
Clinical Significance of the Proposed Pathologic Criteria for Invasion by the International Association for the Study of Lung Cancer in Resected Nonmucinous Lung Adenocarcinoma
Authors: Tae Hee Hong, Soohyun Hwang, Juhee Cho, Yoon-La Choi, Joungho Han, Genehee Lee, Yeong Jeong Jeon, Junghee Lee, Seong Yong Park, Jong Ho Cho, Yong Soo Choi, Jhingook Kim, Young Mog Shim, Hong Kwan Kim
Journal: Journal of Thoracic Oncology (2023)

Accurate diagnostic criteria for tumor invasion are essential for precise pathologic tumor (pT) staging. Recently, the International Association for the Study of Lung Cancer (IASLC) Pathology Committee suggested a new set of criteria for assessing tumor invasion, but the clinical usefulness of the proposed criteria has not been evaluated.
A Fully Automated Deep-Learning Model for Predicting the Molecular Subtypes of Posterior Fossa Ependymomas Using T2-Weighted Images
Authors: Dan Cheng, Zhizheng Zhuo, Jiang Du, Jinyuan Weng, Chengzhou Zhang, Yunyun Duan, Ting Sun, Minghao Wu, Min Guo, Tiantian Hua, Ying Jin, Boyang Peng, Zhaohui Li, Mingwang Zhu, Maliha Imami, Chetan Bettegowda, Haris Sair, Harrison X. Bai, Frederik Barkhof, Xing Liu, Yaou Liu
Journal: Clinical Cancer Research (2023)

Abstract Purpose: We aimed to develop and validate a deep learning (DL) model to automatically segment posterior fossa ependymoma (PF-EPN) and predict its molecular subtypes [Group A (PFA) and Group B (PFB)] from preoperative MR images. Experimental Design: We retrospectively identified 227 PF-EPNs (development and internal test sets) with available preoperative T2-weighted (T2w) MR images and molecular status to develop and test a 3D nnU-Net (referred to as T2-nnU-Net) for tumor segmentation and molecular subtype prediction. The network was externally tested using an external independent set [n = 40; subset-1 (n = 31) and subset-2 (n =9)] and prospectively enrolled cases [prospective validation set (n = 27)]. The Dice similarity coefficient was used to evaluate the segmentation performance. Receiver operating characteristic analysis for molecular subtype prediction was performed. Results: For tumor segmentation, the T2-nnU-Net achieved a Dice score of 0.94 ± 0.02 in the internal test set. For molecular subtype prediction, the T2-nnU-Net achieved an AUC of 0.93 and accuracy of 0.89 in the internal test set, an AUC of 0.99 and accuracy of 0.93 in the external test set. In the prospective validation set, the model achieved an AUC of 0.93 and an accuracy of 0.89. The predictive performance of T2-nnU-Net was superior or comparable to that of demographic and multiple radiologic features (AUCs ranging from 0.87 to 0.95). Conclusions: A fully automated DL model was developed and validated to accurately segment PF-EPNs and predict molecular subtypes using only T2w MR images, which could help in clinical decision-making.